The hypothesis that natural killer (NK) cells play an important role in immune surveillance against tumors has been based on data obtained in mouse experiments in which the results could have been influenced by immunological differences other than those observed in NK activity. There is therefore an obvious need for an in vivo model where animals, without manipulation, differ in NK activity only. The mutant beige mouse, which is NK-deficient, seemed promising until an additional T-cell defect was found. We have investigated the effects on several cellular immune functions of the transfer of nude genes to beige mice. The resulting viable, double homozygous recessive bg/bg nu/nu (beige-nude) mice combine the relative absence of T-cell function in regular nude mice, known to have high NK levels with the very low NK activity of beige mice. Therefore, such double immune deficient mice provide new possibilities for studying immune surveillance, particularly for establishing to what extent NK cells take part in host defense against spontaneous, induced, or transplantable tumors. Interestingly, no spontaneous malignant tumors have so far been observed in beige-nude mice.